The objectives of this study are to ascertain mechanisms of male reproductive disorders and to provide rational strategies of treatment for men with reproductive disease. These include 1) studies of the hormonal regulation of spermatogenesis in hypogonadotropic men, 2) analysis of biochemical parameters of sperm metabolism in men with non-motile sperm, 3) longitudinal evaluation of the adverse effects of cytotoxic drugs on testicular function in men receiving chemotherapy for malignant disorders, and 4) the evaluation of treatment of men with infertility. Studies performed during the past year have shown an important inhibitory effect of estradiol on sperm production in hypogonadotropic men treated with Human Chorionic Gonadotropin and that sperm production can be stimulated in the absence of supplemental FSH by administration of a drug (Teslac) which inhibits estradiol production. By contrast, no such improvement in sperm production or semen quality was shown among men with idiopathic oligospermic infertility. We conclude from these data that the infertility resulting from idiopathic ologospermia is more likely due to abnormalities in sperm function than to an endocrine disorder. In addition, a prospective study of the effect of x-ray exposure on testicular function has been completed among men with soft tissue sarcoma who received radiation therapy. The study shows that testicular exposure to fractionated radiation above 50 R leads to germinal depletion with increased serum FSH. Studies of the rate of testicular recovery are in progress, but the preliminary results indicate that above 100R testicular injury persists at least to 3 years. These data will be extremely important to the practicing oncologist and endocrinologist in view of increased survival rates of cancer patients receiving radiotherapy.